We plan to investigate two aspects of iron nutrition during development in infants and using the rat and the rabbit as experimntal models. 1. The first group of experiments is based on the hypothesis that there are nutritionally significant interactions between iron, zinc, and copper take in the ranges of intake that are most pertinent to human nutrition. If this is the case, such interactions would have particularly important nutritional implications for early development, when trace mineral needs are greatest, when the dietary supply of many minerals is marginal, and when supplementation or fortification with vitamins and minerals might have the greatest potential for harm if inappropriate combinations are used. Healthy one-year-old infants will either receive 3 month of iron supplementation or a placebo. Measurements of trace mineral nutrition and anthropometric measurements will be done before and after therapy. The result of this phase of the study should indicate whether the utilization of zinc and copper in the diet is jeopardized by the use of supplements in which iron is the only mineral. In the next phase, infants will receive either a multivitamin supplement with iron or the same supplement with zinc and copper added, in order to determine whether there is any demonstrable advantage to supplementing ostensibly healthy infants with copper and zinc. Parallel experiments in the rat, will focus on the characteristics of the mineral interactions and their physiologic significance. 2. The second group of experiments deals with the physiological basis for using the measurement of erythrocyte protoporphyrin (EP) in the diagnosis of iron deficiency. EP accumulates when there is insufficient iron for the optimal conversion of EP to heme. It has come to prominence in the detection of iron deficiency because it can be measured within minutes on a small sample blood. EP exists in a free form (FEP) and a zinc-complexed form (ZEP). We plan to use new, refined methods to determine the metabolic basis for alterations in the ratio of FEP to ZEP and to what extent such alterations result in errors in the diagnostic use of the text. These experiments should provide new information on protoporphyrin metabolism and be valuable in clarifying the advantages and limitations of EP in the diagnosis of iron deficiency.